Certain drugs whose molecular structure contains several potential sites for oxidation are selectively hydroxylated by the seemingly non-specific drug-metabolizing systems of mammalian liver microsomes which act upon a broad spectrum of different substrates. It has been generally accepted that binding of the different substrates of ferricytochrome P-450 is a required step in their oxidative catabolism. However it is not clear how these agents are bound, whether the binding is altered by other components of the electron transfer system, nor whether selective oxidation is related to the mode in which the drug is bound. A nuclear magnetic resonance study of the interactions of a variety of chemical substances with several hemoproteins including cytochrome P-450 will be undertaken with the immediate objective of fully characterizing such interactions according to changes in the NMR spectra under various conditions. The results of these studies will aid in the interpretation of data which will be obtained from studies of re-constituted cytochrome P-450 systems which will be directed toward the overall goal of defining the basis for the paradoxical specificity of the P-450 systems. BIBLIOGRAPHIC REFERENCES: J.J. Mieyal, R.S. Ackerman, J.L. Blumer and L.S. Wilson, "Hemoglobin: P-450 Reductase Coupled Hydroxylation," Pharmacologist (1975), p.230. Presented at ASPET Fall Meeting (8/20/75).